Composition and methods are provided for the specific manipulation of protein tyrosine phosphatase (PTP) activity, including without limitation manipulation of protein tyrosine phosphatase receptor type gamma (PTPRG). The modulation of PTP activity can be performed in vitro or in vivo, and is useful for therapeutic and research purposes. In some embodiments, an effective dose of a PTP modulator is provided to an individual for preventing or treating disease involving dysregulated tyrosine kinase activity and/or signaling mechanisms involving tyrosine phosphorylation and/or tyrosine kinase activity. In other embodiments, a PTP modulator is utilized in the analysis and screening of phosphatase pathways in a cell.
